Children with Crohn’s disease who received antitumor necrosis factor-alpha within 3 months of diagnosis experienced better overall clinical and growth outcomes at 1 year, compared with their counterparts who received an immunomodulator or those who received no immunomodulator therapy, results from an observational study demonstrated.
Although the current standard of practice for children recently diagnosed with Crohn’s disease (CD) involves early administration of immunomodulators after initial treatment with corticosteroids, some pediatric gastroenterologists, inspired by data from adult trials, "are adopting earlier introduction of anti-TNF-alpha therapy (without a trial of immunomodulators alone) in patients with inflammatory luminal CD judged to be at risk of serious chronically active disease," researchers led by Dr. Thomas D. Walters wrote in the February issue of Gastroenterology.
Source: American Gastroenterological Association
Dr. Walters of the Hospital for Sick Children in Toronto and his associates went on to note that while the efficacy of anti-TNF-alpha therapy is well established, "it has yet to be shown that the early use of this therapy in a specific group of pediatric patients (those with inflammatory luminal disease) is any more effective at improving patient outcomes than the classic step-up approach." In an effort to answer this question, the researchers analyzed data from the ongoing Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children With Crohn’s Disease (RS) trial, which was launched in 2008 at 28 pediatric gastroenterology centers in North America. The purpose of the current study was to determine whether anti-TNF-alpha monotherapy started within 3 months of diagnosis improves 1-year outcomes, compared with clinically similar patients who were treated with immunomodulator monotherapy started within 3 months of diagnosis or those who were treated with no immunotherapy during that time frame.
The researchers evaluated data from 552 patients who participated in the trial RISK between 2008 and 2012. They used propensity score matching "to avoid the usual problem of confounding by indication when using observational cohort data to explore differences in treatment response." More than half of the patients (61%) were male, their mean age was 11.8 years, and 63% had a Pediatric Crohn’s Disease Activity Index (PCDAI) score of greater than 30. The primary outcome of interest was corticosteroid-free clinical remission (defined as a PCDAI of 10 or less) at 1 year after diagnosis without luminal resection (Gastroenterology 2013 [doi: 10.1053/j.gastro.2013.10.027]).
Of the 552 patients, 68 received early anti-TNF-alpha monotherapy, 248 received early immunomodulator therapy, and 236 received no early immunotherapy. After propensity score matching, 85% of patients treated with early anti-TNF-alpha monotherapy achieved remission at 1 year, compared with 60% of those who were treated with early immunomodulator monotherapy and 54% of those who received no early immunotherapy, a difference that reached statistical significance (P =.0003). When the researchers factored in therapy after 3 months as a covariate, the results did not change; treatment with anti-TNF-alpha monotherapy remained significantly superior to early immunomodulator monotherapy (risk ratio, 1.51; P =.0004), while early immunomodulator monotherapy was no different from no early immunotherapy (RR, 1.00; P =.99).
Dr. Walters and his associates also observed that while weight and body mass index scores improved in all three groups, the height z score only showed improvement in the early anti-TNF-alpha group.
"Although our data clearly have added to the evidence base guiding treatment decisions after a diagnosis of Crohn’s disease in children, they should not be taken as an endorsement of one early therapeutic regimen over another," the authors concluded. "We were not able to identify any common clinical or laboratory characteristic that predicted response or failure with a particular approach. Further genetic, serologic, and microbiome analysis of our study cohort in conjunction with comparative efficacy results will better elucidate the value of different treatment decisions."
The study was supported by the Crohn’s and Colitis Foundation of America. Dr. Walters and many of his coauthors disclosed having received research support, consulting fees, or being on the speakers bureau for numerous pharmaceutical companies.
